Purpose-Immunization with plasmid DNA has been shown to induce protective immunity in a variety of experimental models of infection. The ability of DNA vaccination to elicit both MHC class I and class II restricted T cell responses has been shown to be responsible for mediating these protective immune responses. Thus, DNA vaccination can provide a useful and an effective way in providing effective immunity to particular pathogens depending on the type of immunity required for protection. We have identified a number of murine experimental models in which to develop an understanding for the utility of DNA vaccination. For infectious diseases, this includes murine models for Leishmania major (L. major), Mycobacterium tuberculosis and Influenza. In addition this work is being applied to primate studies using DNA for HIV-specific antigens. The work involves identifying cloned antigens for the specific infectious agent and cloning it into an appropriate euykaryotic expression vector. In addition, we have obtained DNA for a number of cytokines and costimulatory molecules to be used as adjuvants to the specific antigens. Following purification of the DNA, mice are then injected and boosted several weeks later. At various times following the vaccination, mice are infected with a particular pathogen. Parameters that are followed include survival, quantitation of infectious burden, and immunologic studies of antibody and cytokine production.